Nick A Maskell

Investigation of a unilateral pleural effusion in adults: British Thoracic Society pleural disease guideline 2010

Pleural effusions are a common medical problem with more than 50 recognised causes including disease local to the pleura or underlying lung, systemic conditions, organ dysfunction and drugs.1 Pleural effusions occur as a result of increased fluid formation and/or reduced fluid resorption. The precise pathophysiology of fluid accumulation varies according to underlying aetiologies. As the differential diagnosis for a unilateral pleural effusion is wide, a systematic approach to investigation is necessary. The aim is to establish a diagnosis swiftly while minimising unnecessary invasive investigations and facilitating treatment, avoiding the need for repeated therapeutic aspirations when possible. Since the 2003 guideline, several clinically relevant studies have been published, allowing new recommendations regarding image guidance of pleural procedures with clear benefits to patient comfort and safety, optimum pleural fluid sampling and processing and the particular value of thoracoscopic pleural biopsies. This guideline also includes a review of recent evidence for the use of new biomarkers including N-terminal pro-brain natriuretic peptide (NT-proBNP), mesothelin and surrogate markers of tuberculous pleuritis. The history and physical examination of a patient with a pleural effusion may guide the clinician as to whether the effusion is a transudate or an exudate. This critical distinction narrows the differential diagnosis and directs further investigation. Clinical assessment alone is often capable of identifying transudative effusions. Therefore, in an appropriate clinical setting such as left ventricular failure with a confirmatory chest x-ray, such effusions do not need to be sampled unless there are atypical features or they fail to respond to treatment. Approximately 75% of patients with pulmonary embolism and …

Intrapleural Use of Tissue Plasminogen Activator and DNase in Pleural Infection

BACKGROUND More than 30% of patients with pleural infection either die or require surgery. Drainage of infected fluid is key to successful treatment, but intrapleural fibrinolytic therapy did not improve outcomes in an earlier, large, randomized trial. METHODS We conducted a blinded, 2-by-2 factorial trial in which 210 patients with pleural infection were randomly assigned to receive one of four study treatments for 3 days: double placebo, intrapleural tissue plasminogen activator (t-PA) and DNase, t-PA and placebo, or DNase and placebo. The primary outcome was the change in pleural opacity, measured as the percentage of the hemithorax occupied by effusion, on chest radiography on day 7 as compared with day 1. Secondary outcomes included referral for surgery, duration of hospital stay, and adverse events. RESULTS The mean (±SD) change in pleural opacity was greater in the t-PA-DNase group than in the placebo group (-29.5±23.3% vs. -17.2±19.6%; difference, -7.9%; 95% confidence interval [CI], -13.4 to -2.4; P=0.005); the change observed with t-PA alone and with DNase alone (-17.2±24.3 and -14.7±16.4%, respectively) was not significantly different from that observed with placebo. The frequency of surgical referral at 3 months was lower in the t-PA-DNase group than in the placebo group (2 of 48 patients [4%] vs. 8 of 51 patients [16%]; odds ratio for surgical referral, 0.17; 95% CI, 0.03 to 0.87; P=0.03) but was greater in the DNase group (18 of 46 patients [39%]) than in the placebo group (odds ratio, 3.56; 95% CI, 1.30 to 9.75; P=0.01). Combined t-PA-DNase therapy was associated with a reduction in the hospital stay, as compared with placebo (difference, -6.7 days; 95% CI, -12.0 to -1.9; P=0.006); the hospital stay with either agent alone was not significantly different from that with placebo. The frequency of adverse events did not differ significantly among the groups. CONCLUSIONS Intrapleural t-PA-DNase therapy improved fluid drainage in patients with pleural infection and reduced the frequency of surgical referral and the duration of the hospital stay. Treatment with DNase alone or t-PA alone was ineffective. (Funded by an unrestricted educational grant to the University of Oxford from Roche UK and by others; Current Controlled Trials number, ISRCTN57454527.).

Asymptomatic carriage of Pneumocystis jiroveci in subjects undergoing bronchoscopy: a prospective study

Background: The opportunistic fungus Pneumocystis jiroveci is a common cause of respiratory infection in immunocompromised patients. By contrast, pneumocystis pneumonia (PCP) occurs only rarely in immunocompetent individuals. Asymptomatic colonisation with P jiroveci has recently been described in patients who are either minimally immunosuppressed or who have underlying lung disorders such as bronchiectasis. We sought to determine the prevalence of asymptomatic colonisation by P jiroveci in a cohort of adult patients undergoing diagnostic bronchoscopy. Methods: A prospective observational cohort study was performed in patients who required bronchoscopy and bronchoalveolar lavage (BAL) as part of their routine clinical assessment. All the samples underwent standard microbiological analysis and a Grocott methenamine silver stain was performed where clinically indicated to detect the presence of P jiroveci. Polymerase chain reaction for detection of P jiroveci specific DNA was also performed. Results: Ninety three consecutive BAL fluid samples were analysed, 17 (18%) of which contained P jiroveci DNA. Of the potential predictors examined, only glucocorticoid use was significantly associated with detectable P jiroveci DNA. Eighteen patients were receiving oral glucocorticoids (equivalent to >20 mg/day prednisolone) at the time of bronchoscopy, of whom eight (44%) had detectable P jiroveci DNA. In contrast, P jiroveci was detected in only nine of 75 patients (12%) who were not receiving glucocorticoids (difference between proportions 32%, 95% CI 8 to 57; p=0.004, two tailed Fisher’s exact test). Conclusions:P jiroveci colonisation, as determined by detection of P jiroveci DNA in BAL fluid, is common in HIV negative patients with primary respiratory disorders undergoing bronchoscopy and BAL. The higher prevalence in patients receiving corticosteroids suggests that oral glucocorticoid therapy is an independent risk factor for colonisation. In contrast, underlying lung cancer or COPD did not appear to be risk factors.

The Relationship Between Chest Tube Size and Clinical Outcome in Pleural Infection

BACKGROUND The optimal choice of chest tube size for the treatment of pleural infection is unknown, with only small cohort studies reported describing the efficacy and adverse events of different tube sizes. METHODS A total of 405 patients with pleural infection were prospectively enrolled into a multicenter study investigating the utility of fibrinolytic therapy. The combined frequency of death and surgery, and secondary outcomes (hospital stay, change in chest radiograph, and lung function at 3 months) were compared in patients receiving chest tubes of differing size (chi(2), t test, and logistic regression analyses as appropriate). Pain was studied in detail in 128 patients. RESULTS There was no significant difference in the frequency with which patients either died or required thoracic surgery in patients receiving chest tubes of varying sizes ( < 10F, number dying or needing surgery 21/58 [36%]; size 10-14F, 75/208 [36%]; size 15-20F, 28/70 [40%]; size > 20F, 30/69 [44%]; chi(2)trend, 1 degrees of freedom [df] = 1.21, P = .27), nor any difference in any secondary outcome. Pain scores were substantially higher in patients receiving (mainly blunt dissection inserted) larger tubes ( < 10F, median pain score 6 [range 4-7]; 10-14F, 5 [4-6]; 15-20F, 6 [5-7]; > 20F, 6 [6-8]; chi(2), 3 df = 10.80, P = .013, Kruskal-Wallis; chi(2)trend, 1 df = 6.3, P = .014). CONCLUSIONS Smaller, guide-wire-inserted chest tubes cause substantially less pain than blunt-dissection-inserted larger tubes, without any impairment in clinical outcome in the treatment of pleural infection. These results suggest that smaller size tubes may be the initial treatment of choice for pleural infection, and randomized studies are now required. TRIAL REGISTRATION MIST1 trial ISRCTN number: 39138989.

Predicting survival in malignant pleural effusion: development and validation of the LENT prognostic score

Background Malignant pleural effusion (MPE) causes debilitating breathlessness and predicting survival is challenging. This study aimed to obtain contemporary data on survival by underlying tumour type in patients with MPE, identify prognostic indicators of overall survival and develop and validate a prognostic scoring system. Methods Three large international cohorts of patients with MPE were used to calculate survival by cell type (univariable Cox model). The prognostic value of 14 predefined variables was evaluated in the most complete data set (multivariable Cox model). A clinical prognostic scoring system was then developed and validated. Results Based on the results of the international data and the multivariable survival analysis, the LENT prognostic score (pleural fluid lactate dehydrogenase, Eastern Cooperative Oncology Group (ECOG) performance score (PS), neutrophil-to-lymphocyte ratio and tumour type) was developed and subsequently validated using an independent data set. Risk stratifying patients into low-risk, moderate-risk and high-risk groups gave median (IQR) survivals of 319 days (228–549; n=43), 130 days (47–467; n=129) and 44 days (22–77; n=31), respectively. Only 65% (20/31) of patients with a high-risk LENT score survived 1 month from diagnosis and just 3% (1/31) survived 6 months. Analysis of the area under the receiver operating curve revealed the LENT score to be superior at predicting survival compared with ECOG PS at 1 month (0.77 vs 0.66, p<0.01), 3 months (0.84 vs 0.75, p<0.01) and 6 months (0.85 vs 0.76, p<0.01). Conclusions The LENT scoring system is the first validated prognostic score in MPE, which predicts survival with significantly better accuracy than ECOG PS alone. This may aid clinical decision making in this diverse patient population.

Blood culture bottle culture of pleural fluid in pleural infection

Background Pleural infection is common, and has a >30% major morbidity and mortality—particularly when infection is caused by Gram-negative, Staphylococcus aureus or mixed aerobic pathogens. Standard pleural fluid culture is negative in ∼40% of cases. Culturing pleural fluid in blood culture bottles may increase microbial yield, and is cheap and easy to perform. Objectives To determine whether inoculating pleural fluid into blood culture bottles increases the culture positivity of pleural infection over standard laboratory culture, and to assess the optimum volume of inoculum to introduce. Methods 62 patients with pleural infection were enrolled. Pairs of aerobic and anaerobic blood culture bottles were inoculated at the bedside with 2, 5 or 10 ml of pleural fluid, and two pleural fluid specimens were sent for standard culture. Pleural fluid from nine control patients was cultured to test for ‘false-positive’ results. Results The addition of blood culture bottle culture to standard culture increased the proportion of patients with identifiable pathogens by 20.8% (20/53 (37.7%) to 31/53 (58.5%) (difference 20.8%, 95% CI difference 8.9% to 20.8%, p<0.001)). The second standard culture did not similarly improve the culture positivity (19/49 (38.8%) to 22/49 (44.9%) (difference 6.1%, 95% CI difference −2.5% to 6.1%, p=0.08)). The culture inoculum volume did not influence bacterial isolation frequency. The control fluids were culture negative. Conclusions Blood culture bottle culture of infected pleural fluid increases microbial yield when used in addition to standard culture. This technique should be part of routine care.

Clinical Outcomes of Indwelling Pleural Catheter-Related Pleural Infections: An International Multicenter Study

BACKGROUND Indwelling pleural catheters (IPCs) offer effective control of malignant pleural effusions (MPEs). IPC-related infection is uncommon but remains a major concern. Individual IPC centers see few infections, and previous reports lack sufficient numbers and detail. This study combined the experience of 11 centers from North America, Europe, and Australia to describe the incidence, microbiology, management, and clinical outcomes of IPC-related pleural infection. METHODS This was a multicenter retrospective review of 1,021 patients with IPCs. All had confirmed MPE. RESULTS Only 50 patients (4.9%) developed an IPC-related pleural infection; most (94%) were successfully controlled with antibiotics (62% IV). One death (2%) directly resulted from the infection, whereas two patients (4%) had ongoing infectious symptoms when they died of cancer progression. Staphylococcus aureus was the causative organism in 48% of cases. Infections from gram-negative organisms were associated with an increased need for continuous antibiotics or death (60% vs 15% in gram-positive and 25% mixed infections, P = .02). The infections in the majority (54%) of cases were managed successfully without removing the IPC. Postinfection pleurodesis developed in 31 patients (62%), especially those infected with staphylococci (79% vs 45% with nonstaphylococcal infections, P = .04). CONCLUSIONS The incidence of IPC-related pleural infection was low. The overall mortality risk from pleural infection in patients treated with IPC was only 0.29%. Antibiotics should cover S aureus and gram-negative organisms until microbiology is confirmed. Postinfection pleurodesis is common and often allows removal of IPC. Heterogeneity in management is common, and future studies to define the optimal treatment strategies are needed.

PTPN22 and invasive bacterial disease.

Vang et al.1 recently reported that the protein tyrosine phosphatase PTPN22 Trp620 variant is a gain-of-function mutant, resulting in increased PTPN22 phosphatase activity in T cells. This variant is associated with susceptibility to multiple autoimmune diseases, including type 1 diabetes, rheumatoid arthritis, systemic lupus erythematosus and autoimmune thyroid disease2, 3, 4, 5, 6. Based on the observation that Trp620 downregulates T cell responses1, we hypothesized that the PTPN22 R620W polymorphism may be associated with susceptibility to invasive bacterial infection.

ERS task force statement: diagnosis and treatment of primary spontaneous pneumothorax

Primary spontaneous pneumothorax (PSP) affects young healthy people with a significant recurrence rate. Recent advances in treatment have been variably implemented in clinical practice. This statement reviews the latest developments and concepts to improve clinical management and stimulate further research. The European Respiratory Societys Scientific Committee established a multidisciplinary team of pulmonologists and surgeons to produce a comprehensive review of available scientific evidence. Smoking remains the main risk factor of PSP. Routine smoking cessation is advised. More prospective data are required to better define the PSP population and incidence of recurrence. In first episodes of PSP, treatment approach is driven by symptoms rather than PSP size. The role of bullae rupture as the cause of air leakage remains unclear, implying that any treatment of PSP recurrence includes pleurodesis. Talc poudrage pleurodesis by thoracoscopy is safe, provided calibrated talc is available. Video-assisted thoracic surgery is preferred to thoracotomy as a surgical approach. In first episodes of PSP, aspiration is required only in symptomatic patients. After a persistent or recurrent PSP, definitive treatment including pleurodesis is undertaken. Future randomised controlled trials comparing different strategies are required. A European Task Force reviews scientific evidence and suggests future research for primary spontaneous pneumothorax http://ow.ly/MWhuF

Risk reduction in pleural procedures: sonography, simulation and supervision.

Purpose of review Complications from pleural drainage procedures are common, but their incidence is often underrecognized. Significant morbidity and mortality can arise, particularly as a result of poor procedural technique, lack of training and inadequate supervision. This review discusses safety considerations of common pleural procedures, methods for risk minimization and training issues. Recent findings Recent data have identified deaths and significant adverse events associated with pleural drainage procedures. Evidence suggests that significant risk reduction might be achieved by restricting the number of physicians authorized to perform a pleural aspiration to a smaller expert group who have had specific training and regularly perform the procedure. Pleural ultrasound has been shown to increase the accuracy of fluid localization and decrease the risk of postprocedure pneumothorax. Summary Strategies to improve physician training, reduce unnecessary pleural procedures and improve site selection (using pleural ultrasound) may reduce complication rates. Consequently, several international authorities have recently published updated guidelines and educational packages aimed at improving the safety of pleural intervention. Pleural ultrasound has the potential to significantly decrease adverse event rates, but requires specific training and has several possible pitfalls.